224 research outputs found
Embedding massive flavor in ABJM
We add massive fundamental matter to the ABJM model by adding D6-branes
wrapped asymptotically over RP3. We find two types of solutions at finite
temperature, one that enters the black hole and one that ends before the black
hole. We analyze the behavior of the free energy as a function of temperature,
and find that the system exhibits a phase transition between the two types of
solutions, similar to what happens in the D3-D7 system. We also analyze the
meson spectrum in the model and find several massive scalar modes, again, quite
like the D3-D7 system. We end with a calculation of the conductivities in the
two phases.Comment: 26 pages, 6 figures; version published in JHE
Frailty as a Predictor of Poor Rehabilitation Outcomes among Older Patients Attending a Geriatric Day Hospital Program: An Observational Study.
BACKGROUND
The Geriatric Day Hospital (GDH) is an important outpatient geriatric service, but there are few data on the role of frailty as a potential predictor of poor outcomes in this setting.
METHODS
Data were analyzed from 499 patients aged â„ 60 years attending a 12-week GDH program between 2018 and 2021. Frailty status was defined as non-frail (68, 13.6%), mild/moderate frailty (351, 70.3%), and severe frailty (80, 16.0%) based on the Clinical Frailty Scale (CFS). Outcomes were defined as (1) poor outcome (hospital readmission, death, or medical deterioration) during the program and (2) admission to permanent nursing home care upon completion of the program. Multivariate logistic models were used for predictive analyses.
RESULTS
The mean age was 80.3 (standard deviation 7.0); 58.3% were women. Overall, 77 patients (15.4%) had a poor outcome, and 48 (9.6%) were admitted to permanent nursing home care. Poor outcome was experienced by none of the non-frail patients (0%), by 49 (14.0%) patients with mild/moderate frailty, and 22 (27.5%) patients with severe frailty (adjusted OR, 2.0; 95% CI 1.3, 3.2; p < 0.01). Admission to a permanent nursing home care was experienced by none of the non-frail patients (0%), 20 (5.7%) of those with mild/moderate frailty, and 28 (35.0%) with severe frailty (adjusted OR, 2.9; 95% CI 1.3, 6.3; p < 0.01).
CONCLUSIONS
The CFS is a promising risk predictor of poor outcome and admission to permanent nursing home discharge among older patients attending a GDH program
Mediterranean Founder Mutation Database (MFMD): Taking Advantage from Founder Mutations in Genetics Diagnosis, Genetic Diversity and Migration History of the Mediterranean Population
The Mediterranean basin has been the theater of migration crossroads followed by settlement of several societies and cultures in prehistoric and historical times, with important consequences on genetic and genomic determinisms. Here, we present the Mediterranean Founder Mutation Database (MFMD), established to offer web-based access to founder mutation information in the Mediterranean population. Mutation data were collected from the literature and other online resources and systematically reviewed and assembled into this database. The information provided for each founder mutation includes DNA change, amino-acid change, mutation type and mutation effect, as well as mutation frequency and coalescence time when available. Currently, the database contains 383 founder mutations found in 210 genes related to 219 diseases. We believe that MFMD will help scientists and physicians to design more rapid and less expensive genetic diagnostic tests. Moreover, the coalescence time of founder mutations gives an overview about the migration history of the Mediterranean population. MFMD can be publicly accessed from http://mfmd.pasteur.ma
K Corrections For Type Ia Supernovae and a Test for Spatial Variation of the Hubble Constant
Cross-filter K corrections for a sample of "normal" Type Ia supernovae (SNe)
have been calculated for a range of epochs. With appropriate filter choices,
the combined statistical and systematic K correction dispersion of the full
sample lies within 0.05 mag for redshifts z<0.7. This narrow dispersion of the
calculated K correction allows the Type Ia to be used as a cosmological probe.
We use the K corrections with observations of seven SNe at redshifts 0.3 < z
<0.5 to bound the possible difference between the locally measured Hubble
constant (H_L) and the true cosmological Hubble constant (H_0).Comment: 6 pages, 3 Postscript figures, uuencoded uses crckapb.sty and
psfig.sty. To appear in Thermonuclear Supernovae (NATO ASI), eds. R. Canal,
P. Ruiz-LaPuente, and J. Isern. Postscript version is also available at
http://www-supernova.lbl.gov
Implications For The Hubble Constant from the First Seven Supernovae at z >= 0.35
The Supernova Cosmology Project has discovered over twenty-eight supernovae
(SNe) at 0.35 <z < 0.65 in an ongoing program that uses Type Ia SNe as
high-redshift distance indicators. Here we present measurements of the ratio
between the locally observed and global Hubble constants, H_0^L/H_0^G, based on
the first 7 SNe of this high-redshift data set compared with 18 SNe at z <= 0.1
from the Calan/Tololo survey. If Omega_M <= 1, then light-curve-width corrected
SN magnitudes yield H_0^L/H_0^G < 1.10 (95% confidence level) in both a
Lambda=0 and a flat universe. The analysis using the SNe Ia as standard candles
without a light-curve-width correction yields similar results. These results
rule out the hypothesis that the discrepant ages of the Universe derived from
globular clusters and recent measurements of the Hubble constant are
attributable to a locally underdense bubble. Using the
Cepheid-distance-calibrated absolute magnitudes for SNe Ia of Sandage (1996},
we can also measure the global Hubble constant, H_0^G. If Omega_M >= 0.2, we
find that H_0^G < 70 km/s/Mpc in a Lambda=0 universe and H_0^G < 78 km/s/Mpc in
a flat universe, correcting the distant and local SN apparent magnitudes for
light curve width. Lower results for H_0^G are obtained if the magnitudes are
not width corrected.Comment: 13 pages, 2 Postscript figures. Preprint also available at
http://www-supernova.lbl.gov . To appear in ApJ Letter
Restoring tumour selectivity of the bioreductive prodrug pr-104 by developing an analogue resistant to aerobic metabolism by human aldo-keto reductase 1c3
PR-104 is a phosphate ester pre-prodrug that is converted in vivo to its cognate alcohol, PR-104A, a latent alkylator which forms potent cytotoxins upon bioreduction. Hypoxia selectivity results from one-electron nitro reduction of PR-104A, in which cytochrome P450 oxidoreductase (POR) plays an important role. However, PR-104A also undergoes âoff-targetâ two-electron reduction by human aldo-keto reductase 1C3 (AKR1C3), resulting in activation in oxygenated tissues. AKR1C3 expression in human myeloid progenitor cells probably accounts for the dose-limiting myelotoxicity of PR-104 documented in clinical trials, resulting in human PR-104A plasma exposure levels 3.4- to 9.6-fold lower than can be achieved in murine models. Structure-based design to eliminate AKR1C3 activation thus represents a strategy for restoring the therapeutic window of this class of agent in humans. Here, we identified SN29176, a PR-104A analogue resistant to human AKR1C3 activation. SN29176 retains hypoxia selectivity in vitro with aerobic/hypoxic IC(50) ratios of 9 to 145, remains a substrate for POR and triggers ÎłH2AX induction and cell cycle arrest in a comparable manner to PR-104A. SN35141, the soluble phosphate pre-prodrug of SN29176, exhibited superior hypoxic tumour log cell kill (>4.0) to PR-104 (2.5â3.7) in vivo at doses predicted to be achievable in humans. Orthologues of human AKR1C3 from mouse, rat and dog were incapable of reducing PR-104A, thus identifying an underlying cause for the discrepancy in PR-104 tolerance in pre-clinical models versus humans. In contrast, the macaque AKR1C3 gene orthologue was able to metabolise PR-104A, indicating that this species may be suitable for evaluating the toxicokinetics of PR-104 analogues for clinical development. We confirmed that SN29176 was not a substrate for AKR1C3 orthologues across all four pre-clinical species, demonstrating that this prodrug analogue class is suitable for further development. Based on these findings, a prodrug candidate was subsequently identified for clinical trials
The Type Ia Supernova Rate at z ~ 0.4
We present the first measurement of the rate of Type Ia supernovae at high
redshift. The result is derived using a large subset of data from the Supernova
Cosmology Project as described in more detail at this meeting by Perlmutter et
al. (1996). We present our methods for estimating the numbers of galaxies and
the number of solar luminosities to which the survey is sensitive, the
supernova detection efficiency and hence the control time. We derive a
rest-frame Type Ia supernova rate at z~0.4 of 0.82^+0.54_-0.37 ^+0.42_-0.32 h^2
SNu where the first uncertainty is statistical and the second includes
systematic effects.Comment: 9 pages, 3 Postscript figures, uuencoded uses crckapb.sty and
psfig.sty. To appear in Thermonuclear Supernovae (NATO ASI), eds. R. Canal,
P. Ruiz-LaPuente, and J. Isern. Postscript version is also available at
http://www-supernova.lbl.gov
Scheduled Discoveries of 7+ High-Redshift Supernovae: First Cosmology Results and Bounds on q_0
Our search for high-redshift Type Ia supernovae discovered, in its first
years, a sample of seven supernovae. Using a "batch" search strategy, almost
all were discovered before maximum light and were observed over the peak of
their light curves. The spectra and light curves indicate that almost all were
Type Ia supernovae at redshifts z = 0.35 -- 0.5. These high-redshift supernovae
can provide a distance indicator and "standard clock" to study the cosmological
parameters q_0, Lambda, Omega_0, and H_0. This presentation and the following
presentations of Kim et al. (1996), Goldhaber et al. (1996), and Pain et al.
(1996) will discuss observation strategies and rates, analysis and calibration
issues, the sources of measurement uncertainty, and the cosmological
implications, including bounds on q_0, of these first high-redshift supernovae
from our ongoing search.Comment: 15 pages, 6 Postscript figures, uuencoded uses crckapb.sty and
psfig.sty. To appear in Thermonuclear Supernovae (NATO ASI), eds. R. Canal,
P. Ruiz-LaPuente, and J. Isern. Postscript version is also available at
http://www-supernova.lbl.gov
The Type Ia Supernova Rate at z
We present the first measurement of the rate of Type Ia supernovae at high
redshift. The result is derived using a large subset of data from the Supernova
Cosmology Project. Three supernovae were discovered in a surveyed area of 1.7
square degrees. The survey spanned a week baseline and used images
with limiting magnitude of . We present our methods for
estimating the numbers of galaxies and the number of solar luminosities to
which the survey is sensitive, and the supernova detection efficiency which is
used to determine the control time, the effective time for which the survey is
sensitive to a Type Ia event. We derive a rest-frame Type Ia supernova rate at
of SNu (1 SNu
= 1 SN per century per \Lbsun), where the first uncertainty is
statistical and the second includes systematic effects. For the purposes of
observers, we also determine the rate of SNe, per sky area surveyed, to be SNe\ for SN magnitudes in
the range .Comment: 33 pages, To be published in December 10, 1996 issue of ApJ Vol 47
Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer.
BACKGROUND
Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC).
METHODS
Using gene expression databases we investigated ADAM12 expression in CRC and delineated the source of ADAM12 expression. The clinical value of ADAM12 was retrospectively assessed in the CAIRO2 trial in metastatic CRC with 235 patients (31% of total cohort), and an independent rectal cancer cohort (nâ=â20).
RESULTS
ADAM12 is expressed by activated CRC associated fibroblasts. In the CAIRO2 trial cohort, ADAM12 serum levels were prognostic (ADAM12 low versus ADAM12 high; median OS 25.3 vs. 17.1âmonths, HR 1.48 [95% CI 1.11-1.96], Pâ=â0.007). The prognostic potential was specifically high for metastatic rectal cancer (HR 1.78 [95% CI 1.06-3.00], Pâ=â0.030) and mesenchymal subtype tumors (HR 2.12 [95% CI 1.25-3.60], Pâ=â0.004). ADAM12 also showed potential for predicting recurrence in an exploratory analysis of non-metastatic rectal cancers.
CONCLUSIONS
Here we describe a non-invasive marker for activated stroma in CRC which associates with poor outcome, especially for primary cancers located in the rectum
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